Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

2

Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.

3

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.

4

Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, New York.

5

School of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.

6

Department of Psychology, University of Groningen, Groningen, the Netherlands.

7

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York7Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at.

Abstract

IMPORTANCE:

Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition.

OBJECTIVE:

To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD.

DESIGN, SETTING, AND PARTICIPANTS:

Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements.

INTERVENTIONS:

MAIN OUTCOMES AND MEASURES:

The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale-Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression-Severity and -Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale.

RESULTS:

Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms.

CONCLUSIONS AND RELEVANCE:

This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition.